Abstract The overall objective of this proposal is to develop G protein-based respiratory syncytial virus (RSV) vaccine. RSV is the most common cause of lower respiratory illness in infants and young children worldwide. It also plays significant role in respiratory illness in the elderly and in immunocompromised patients. There is an urgent need and compelling reasons to develop RSV vaccine. Past and current development efforts are mainly focused on F protein-based recombinant vaccines and live attenuated vaccines. Despite major efforts for several decades, an effective RSV vaccine remains elusive. RSV G protein is responsible for viral attachment to host cells. However, only a single G-based vaccine has been studied in humans to date. Concern over the high variability across RSV strains and limited knowledge in its surface structure and in vitro function have contributed to its limited use as vaccine candidate. Recent advances in understanding the roles of G in viral infection and in disease indicate that G should be recognized as an important target for vaccine development. Preliminary studies indicate that our G protein- based vaccine can provide protection against RSV infection in the animal models. Furthermore, we have applied a rational design approach to generate candidates that have high potential to induce broad protection. The main objective of this SBIR proposal is to rigorously evaluate the candidates in two animal models. The proposed work will provide a critical foundation to move the G protein-based RSV vaccine candidate toward clinical study.